Demographic and Clinical Data

In total, 15 patients were included in the evaluation. All patients had a hyperinflammatory condition with an IL-6 concentration > 500 pg/ml at the initiation of therapy. The intended duration of CS therapy was 12 h, which was attained in 11 patients. The extracorporeal circuit clotted in two patients between 6 and 12 h and two patients deceased between 6 and 12 h of therapy, so the last data point after 12 h is missing in those four patients. The mean age was 57 years and 80% were male. The mean Simplified Acute Physiology Score II (SAPS II) on the day of the CS treatment was 69 points and the 28-day mortality rate was 73.3%. The reasons for the hyperinflammatory condition were in descending order: intestinal ischemia (26.7%), acute respiratory distress syndrome, septic shock or compartment syndrome (each 20%), and pancreatitis or necrotizing fasciitis (6.7% each). All patients needed vasopressor support, whereby no significant change in dosage was observed during the application of CS. All patients were treated with anti-infective therapy, 80% with hydrocortisone, and 60% underwent surgical infection control. Detailed patient characteristics and laboratory parameters measured immediately before initiation of CS can be found in Table 2.

Table 2 Patient characteristics and laboratory measurementsClearance of Different Pro-inflammatory Modulators

A total of 13 particularly pro-inflammatory modulators were measured. It was not possible to obtain a quantitative result for each single parameters in all patients because the measurement results fell below the lower limit of quantification. The number of analyzed patients with complete measurement series is shown for each of the parameters (i.e., n = 9). Wilcoxon test with associated samples was used in the absence of a normal distribution. Supplemental Tables S1–S19 present detailed results of the measured mediators in each patient.

Interleukins

A significant (p < 0.02) extracorporeal IL-1β reduction (n = 9) was observed in the first 6 h of treatment. Furthermore, a significant extracorporeal reduction was also observed for IL-6 (n = 15, p < 0.03) and for IL-8 (n = 15, p < 0.01) in the first 3 h of application. As the IL-2 measurement was only possible in four patients, a statistical analysis was not rational. The median (IQR) clearance (ml/min) of the three interleukins IL-1β, IL-6, and IL-8 was 10 min after initiation 114 (77–125), 78 (74–123), and 91 (84–164) ml/min, and decreased significantly (p < 0.01) to 37 (16–42), 14 (9–18), and 33 (24–43) after 6 h, respectively.

IFN-γ, TNF-α, and VEGF

There was a significant (p < 0.01) extracorporeal reduction of IFN-γ (n = 12) in the first 6 h of treatment, of VEGF (n = 15, p < 0.02) in the first 3 h of treatment, and of TNF-α in the first 10 min of treatment (n = 15, p = 0.015). The median (IQR) clearance (ml/min) of IFN-γ, TNF-α, and VEGF was 10 min after initiation 84 (57 – 113), 30 (− 12 to 77), and 83 (65 to 92) ml/min, and decreased significantly (p < 0.01) to 24 (6 to 36), 6 (− 44 to 18), and 13 (− 13 to 45) after 6 h, respectively.

Chemokines

A significant extracorporeal reduction of interferon gamma-induced protein (IP-10) (n = 15, p < 0.01) and monocyte chemoattractant protein-1 (MCP-1) (n = 15, p < 0.01) was detected at all timepoints; macrophage inflammatory proteins 1a (MIP-1a) (n = 15, p < 0.01) was only significantly adsorbed in the first 6 h and normal T cell expressed and secreted (RANTES) (n = 15, p = 0.047) in the first hour of treatment. The median (IQR) clearance (ml/min) of IP-10, MCP-1, MIP-1a, and RANTES was 10 min after initiation 100 (98–212), 72 (71–94), 96 (89–183), and 43 (− 30 to 81) ml/min, and decreased to 87 (78–103), 19 (13–26), 37 (29–46), and − 29 (− 62 to 17) after 6 h, respectively (significant decrease for IP-10 and MCP-1 (p < 0.01)). Higher RANTES concentrations were observed post-CS compared to pre-CS from 1 h of application, resulting in a negative clearance.

Soluble Cell Adhesion Molecules

There was a significant extracorporeal reduction of intercellular adhesion molecule (ICAM) (n = 15, p < 0.04) as well as vascular cell adhesion molecule (VCAM) (n = 15, p < 0.05) in the first 6 h. The median (IQR) clearance (ml/min) of ICAM and VCAM was 10 min after initiation 30 (15–43) and 22 (15–37) ml/min, and decreased to 9 (2–11) and 11 (1–15) after 6 h, respectively (significant decrease p < 0.01 for ICAM). Figure 2 illustrates the median clearance of all pro-inflammatory mediators at the defined timepoints.

Fig. 2

Median clearance of the adsorber for different pro-inflammatory mediators. IL interleukin, IFN interferon, TNF tumor necrosis factor, VEGF vascular endothelial growth factor, IP-10 interferon gamma-induced protein 10, MCP-1 monocyte chemoattractant protein-1, MIP-1 macrophage inflammatory protein-1, RANTES regulated upon activation, normal T cell expressed and secreted, ICAM intercellular adhesion molecule, VCAM vascular cell adhesion molecule

Clearance of Different Anti-inflammatory MediatorsInterleukins

There was a significant extracorporeal IL-4 (n = 11, p < 0.02) and IL-5 (n = 14, p < 0.05) reduction in the first 6 h of treatment as well as IL-10 (n = 14, p < 0.01) reduction in the total 12 h of treatment. The median (IQR) clearance (ml/min) of IL-4, IL-5, and IL-10 was 10 min after initiation 74 (63–115), 86 (66–99), and 102 (78–151) ml/min, and decreased significantly (p < 0.01) to 26 (22–43), 11 (0–41), and 32 (26–45) after 6 h, respectively.

Growth Factors

A significant extracorporeal reduction of fibroblast growth factor (FGF-basic) (n = 9, p < 0.04) was observed in the first 6 h and of platelet-derived growth factor (PDGF) (n = 14, p < 0.01) after 10 min of treatment. As a sufficient measurement of granulocyte/macrophage colony-stimulating factor (GM-CSF) was only possible in four patients, no statistical analysis was performed. The median (IQR) clearance (ml/min) of FGF-basic and PDGF was 10 min after initiation 70 (55–95) and 87 (65–132) ml/min, and decreased significantly (p < 0.01) to 34 (19–39) and 5 (− 39 to 25) after 6 h, respectively. Figure 3 illustrates the median clearance of all anti-inflammatory mediators at the defined timepoints.

Fig. 3

Median clearance of the adsorber for different anti-inflammatory mediators. IL interleukin, FGF fibroblast growth factor, PDGF platelet-derived growth factor

Change in Patients’ Blood

Table 3 displays the median relative change after 6 and 12 h of treatment of the different mediators in patients’ blood.

Table 3 Relative change (%) of different pro- and anti-inflammatory mediators in patients’ blood during CytoSorb® application

Figure 4 illustrates the relative change of key pro- and anti-inflammatory mediators during CS application in patients’ blood.

Fig. 4

Relative change (%) of pro- and anti-inflammatory mediators during CytoSorb® application. IL interleukin, TNF tumor necrosis factor. The boxes of the boxplots represent the interquartile range (IQR) and the line the median. Whiskers were limited to 1.5 times the IQR. The cross represents the mean